Spontaneous and interleukin-2-modulated cytokine release by bronchoalveolar cells in pulmonary malignancy.
In a recent phase I study of inhalative, human natural interleukin-2 (hnIL-2) treatment of pulmonary metastases from previously resected solid tumors (mainly renal carcinoma), we have reported that this treatment resulted in an increased accessory function of alveolar macrophages (AM) [1]. Encouraged by these data, we investigated the influence of hnIL-2 inhalation on proinflammatory cytokines spontaneously released by AM. Bronchoalveolar lavage was performed in four groups, each of four patients, before and after 2 weeks of daily inhalation of 0, 200,000, 600,000 and 1,200,000 IU of hnIL-2, respectively. Bronchoalveolar cells were cultured without stimulation to allow spontaneous release over a period of 24 h, into the supernatant. Concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) were determined by the ELISA technique. Before hnIL-2 inhalation, we measured the following spontaneous cytokine release: TNF-alpha: 1,115.4 +/- 469.1 pg/ml, IL-6: 267.5 +/- 67.7 pg/ml cells, IL-8: 137.8 +/- 40.5 ng/ml, MIP-1alpha: 9.5 +/- 6.8 ng/ml. Inhalation of hnIL-2 did not result in any significant changes in these cytokines. Comparing TNF-alpha release in healthy controls (250.6 +/- 46.7 pg/ml) with that of tumor patients (1,115.4 +/- 469.1 pg/ml), we observed significantly (p < 0.05) elevated TNF-alpha levels in the patient group, which did not change significantly in response to IL-2 inhalation. Our data demonstrate that the activation of AM previously observed after hnIL-2 inhalation is not directly related to a hnIL-2-induced cytokine release by bronchoalveolar cells.
Gaede
K I
KI
Research Centre Borstel, Medical Hospital, Germany.
Zissel
G
G
Schwuléra
U
U
Struff
W G
WG
Lorenz
J
J
Aulitzky
W E
WE
Zipfel
P
P
Schrum
S
S
Schlaak
M
M
Huber
C
C
Müller-Quernheim
J
J
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha